Project Summary/Abstract Osteoarthritis (OA) is a prevalent and debilitating age-related health condition contributing toward physical and psychosocial decline, reduced quality of life, and rising national expenses. Considerable evidence demonstrates health disparities in the burdens of living with OA. Specifically, African Americans with knee OA experience greater clinical pain, functional limitations, and decreased quality of life compared to non-Hispanic whites. Pain is a key factor contributing to functional limitations and physical disability. Psychosocial stress predicts the onset of chronic pain and living with chronic pain contributes to increased psychosocial stress. Ethnic groups differ in environmental and sociocultural stress exposures. Importantly, the body is designed to adapt and strengthen with adequate recovery in response stress. However, persistent stress can take a toll on the system resulting in dysregulation and dysfunction known as allostatic load. Persistent stress and chronic pain contribute toward altered functioning across multiple biological systems including the brain. Structural and functional changes and accelerated aging in the brain have been observed among individuals with chronic pain, including those with knee OA. Altered stress-related biological functioning has also been indicated in individuals with chronic pain. These biological changes likely contribute to increased morbidity and mortality among those with chronic pain and OA. What is not known however is whether: 1) African Americans and non- Hispanic whites with knee OA differ across biological measures of aging, 2) biological measures of aging are inter-related, and 3) biological measures of aging predict ethnic group differences in osteoarthritis-related health outcomes. Importantly, there is evidence that health promoting behaviors and psychosocial factors may modulate the biological consequences of OA-related pain and stress. We will investigate a comprehensive array of biopsychosocial measures across three time points in a four year longitudinal analysis of 200 adults with knee OA (100 African Americans and 100 non-Hispanic whites) to determine the influence of stress exposure on measures of biological aging (allostatic load, telomere length, and brain structure/function), and the relationship between biological measures of aging and ethnic group differences in knee OA health outcomes. We will also evaluate the possible modulating effect of risk and resilience factors. Findings will 1) contribute to an improved understanding of the stress, resilience, aging, and health outcome dynamic; 2) promote the identification of biological markers sensitive to stress related exposure and indicative of health- related system functioning; and 3) elucidate resilience factors that may serve as clinical targets to reduce ethnic group disparities in OA and improve overall health outcomes.